Sodium Carbonate → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2'-methoxy-3,6'-dimethyl-2,4'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 869935Notes

Reaction equation

HRID 869935 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[CH:4][C:3]=1[CH3:25].[CH3:26][O:27][C:28]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[C:30]([CH3:43])[N:29]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:32]5[CH:31]=[C:30]([CH3:43])[N:29]=[C:28]([O:27][CH3:26])[CH:33]=5)[C:3]([CH3:25])=[CH:4][CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 467393212-Methoxy-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide

Product 1

HCID 687378231-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2'-methoxy-3,6'-dimethyl-2,4'-bipyridin-6-yl)cyclopropanecarboxamideYield 86.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (200 mg, 0.545 mmol), 2-methoxy-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (408 mg, 1.636 mmol) and tetrakis(triphenylphosphine)palladium (0) (64 mg, 0.055 mmol) in 1,2-dimethoxyethane (3.3 mL), 2 M Na2CO3 (818.0 μL, 1.63 mmol) was added. The reaction mixture was stirred and heated at 80° C. for 68 hours under N2 atmosphere. The reaction mixture was diluted with ethyl acetate (5 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-15% ethyl acetate in hexane) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-3,6′-dimethyl-2,4′-bipyridin-6-yl)cyclopropanecarboxamide (214 mg, 86.5%). ESI-MS m/z calc. 453.4. found 454.5 (M+1)+, retention time 1.81 minutes.

Workup

  1. dry with materialdried over Na2SO4
  2. filtrationfiltered
  3. customevaporated under reduced pressure
  4. customThe crude product was purified by column chromatography on silica gel (0-15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-29d5f999fcc9469482e8ddb98ab0a5f7
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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